Fibronectin-containing ophthalmic solution, method of preserving an opthalmic solution, and methods of treatment of opthalmic wounds

Abstract

A stable and soluble multi-dose ophthalmic solution is disclosed. The solution contains fibronectin, an amino acid, a sugar, and a lower alkyl p-hydroxybenzoate. A method treatment of ophthalmic wounds employing the ophthalmic solution, a process for preparing fibronectin for ophthalmic use, a method of lyophilizing an aqueous solution of fibronectin free of albumin, a method for inhibiting bacterial growth in an ophthalmic solution while preserving the cellular adhesion and wound healing activities of fibronectin, and a method of treatment of ophthalmic wounds administering a wound-healing accelerator solution are also disclosed.

We claim: 
     
       1. A method of treatment of ophthalmic wounds comprising administering to the wound a wound healing accelerator solution disposed in a multi-use container, wherein said solution comprises a wound healing accelerator, wherein the wound healing accelerator is fibronectin, epithelial growth factor, or fibroblast growth factor, and a lower alkyl p-hydroxybenzoate preservative, and said wound healing accelerator solution is free of albumin. 
     
     
       2. The method of claim 1, wherein the ophthalmic solution further comprises a potentiating agent selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof. 
     
     
       3. The method of claim 2, wherein the lower alkyl p-hydroxybenzoate preservative comprises a combination of ethyl p-hydroxybenzoate and butyl p-hydroxybenzoate, together with disodium dihydrate ethylenediaminetetraacetate. 
     
     
       4. An ophthalmic solution for application to ophthalmic wounds comprising a wound healing accelerator and a lower alkyl p-hydroxybenzoate preservative, wherein the wound healing accelerator is fibronectin, epithelial growth factor, or fibroblast growth factor, said ophthalmic solution being free of albumin. 
     
     
       5. The ophthalmic solution of claim 4, wherein the lower alkyl p-hydroxybenzoate preservative is from 0.002 to 0.25 % (w/v). 
     
     
       6. The ophthalmic solution of claim 4, wherein the lower alkyl p-hydroxybenzoate preservative comprises methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, or mixtures thereof. 
     
     
       7. The ophthalmic solution of claim 4, wherein the wound healing accelerator is fibronectin and the concentration of fibronectin is from 0.25 to 10.0 mg/ml. 
     
     
       8. The ophthalmic solution of claim 4, further comprising a potentiating agent selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof. 
     
     
       9. The ophthalmic solution of claim 8, wherein the salts of ethylenediaminetetraacetic acid comprise disodium ethylenediaminetetraacetate and disodium dihydrate ethylenediaminetetraacetate. 
     
     
       10. The ophthalmic solution of claim 8, wherein the lower alkyl p-hydroxybenzoate preservative comprises a combination of ethyl p-hydroxybenzoate and butyl p-hydroxybenzoate, together with disodium dihydrate ethylenediaminetetraacetate. 
     
     
       11. The ophthalmic solution of claim 10, wherein the concentration of ethyl p-hydroxybenzoate is from 0.005 to 0.17 %, the concentration of butyl p-hydroxybenzoate is from 0.002 to 0.02%, and the concentration of disodium dihydrate ethylenediaminetetraacetate is from 0.005 to 0.1%. 
     
     
       12. A method for inhibiting bacterial growth in an ophthalmic solution comprising a wound healing accelerator wherein the wound healing accelerator is fibronectin, epithelial growth factor, or fibroblast growth factor, and said ophthalmic solution is free of albumin, said method comprising adding to said ophthalmic solution a lower alkyl p-hydroxybenzoate preservative in an amount sufficient to inhibit bacterial growth in said ophthalmic solution, while preserving the wound healing properties of the wound healing accelerator.